Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments.

Assessment of thymus size in healthy term neonates using sonography - A study from tertiary care hospital of Central India.

OBJECTIVE: A cross-sectional study was done to assess the size of thymus in term healthy infants using sonography and to assess its variation in size, shape, location, echogenicity and echotexture for both male and female reference population. MATERIAL AND METHODS: A total of 250 term healthy neonates of either sex were subjected to thymic sonography. The shape, size in maximal anteroposterior, longitudinal, and transverse dimensions of both right and left lobes of thymus was evaluated. Their echotexture and echogenicity were determined and standards for reference population were calculated. The results were statistically evaluated. RESULTS: According to the shape; the thymus was quadrilateral in 156 neonates (62%), round in 37 (15%), bilobate in 32 (13%), and crescent shaped in 25 (10%) in transverse scan. According to the echo texture, the thymus echogenicity was homogeneous and almost similar or slightly less to that of the liver and spleen in most cases 200 [80%] and was coarse in 50 (20%). In all subjects, the echogenicity of the thymus was less than that of the thyroid gland. Variations in location of the thymus were found in 70 (28%) neonates. The range of mean AP diameter was 0.39-2.36 cm (mean 1.43 ± 0.3), that of transverse 1.4 - 4.3 cm (mean 2.16 ± 0.54) and that of thymic index 1.2-5.1 cm2 (mean 2.98 ± 0.64). CONCLUSIONS: A normative range was calculated for standard population, which can be used as a reference for comparing thymus size for both normal and diseased neonates for various immunological diseases.

Assessment of the thymic morphometry using ultrasound in full-term newborns.

PURPOSE: The size of thymus is variable and depends on age of the individual. Thymus undergoes its maximum development at the time of birth, when it also has the greatest relative weight. The aim of our study was to compare the two ways of expressing the size of the newborns' thymus, the Thymus index and estimated volume of thymus. METHODS: The examined group consisted of 212 full-term newborns from Slovakia, Europe. We estimated the length, width and thickness of the left and right lobes. We used these data to calculate the approximate volume of the thymus. We also expressed size of the thymus as a multiple of the transverse diameter of the cranial part of the thymus and the sagittal area of the larger lobe of the thymus, the so-called Thymus index. Bilateral differences in thymus lobes' sizes, as well as the thymus' sizes between sexes and among the newborns of different types of birth were also analysed. RESULTS: Our results show that (1) the left thymus lobe is longer and thicker than the right lobe; (2) the Thymus index and the estimated volume of the thymus have a strong significant and positive correlation; (3) boys reach significantly higher values of the Thymus index than girls; and (4) when comparing the differences in the thymus size between the newborns born in two different ways (spontaneous and operatively), no significant difference was discovered. CONCLUSION: Ultrasound examination is safe, effective and suitable for simple assessment of the thymus size, which has a great variability in children. In other hand, the use of the Thymus index in everyday clinical practice is limited due to different mean values in a number of studies.

Evaluación del tamaño del timo: validez y confiabilidadde la ecografía del timo en niños / Assessment of the size of the thymus: validity and reliability of ultrasonography of the thymus in children

El propósito del trabajo fue establecer la validez y confiabilidad de la Ecografía del Timo en niños menores de 6 años de edad, de ambos sexos, en la actualidad es una de las herramientas que puede evaluar la función de la respuesta inmunitaria en forma confiable yno invasiva. Metodos. La validez de la ultrasonografía del timo, es demostrada frente aun patrón de oro, en niños fallecidos se ejecutó la ecografía vs. la Anatomía Patológica (Grupo 1); y en otros niños la ecografía vs. laTomografía Axial Computarizada (TAC)(Grupo 2). La confiabilidad, fue evaluada a nivel intra observador (Grupo 3), se evaluó su estado nutricional mediante: peso para talla, peso para la edad, talla para la edad. A todos los niños, con evaluación de la TAC yla confiabilidad se les realizó un examen y un cuestionario de tipo clínico pediátrico. Resultados. Tanto la evaluación por anatomía patológica (n=5), como por tomografía axial computarizada (n=4) vs. la ecografía del timo no muestran diferencias estadísticamente signifi cativas en la mediciones realizadas en el tamaño del timo en los niños evaluados. En el grupo 3 (n=15), el índice de correlación intraclase es de 0.96. Se realizaron los cálculos de One-way ANOVA + test de Scheffe y elanálisis de varianza (ANOVA). Conclusion. La validez de la ecografía del timo en niños es adecuada, esuna herramienta que “mide lo que dice medir”. La confi abilidad intraobservador, establece un índice de correlación casi perfecto conun personal adecuadamente entrenado para medir con la ecografía el timo en niños.

Abstract. Evaluation of the thymus size: validity and reliableness of thymussonography in children. Introduction. The porpuse of this paper was to stablish the validity and the reliableness of thymus sonography in children under 6 years of age of both sexes. At present, thymus songraphy is one of the tools for assessing the function of the immune response by means of a reliable and non-invasive method. Methods. The validity of thymus ultrasongraphy is demonstrated in front of a gold standard, in dead children, sonography was performed and compared to pathological anatomy (group 1); and in other children, sonography was compared to computerized axial tomography (TAC) (group 2). The reliableness was evaluated at the intraobserver level (group 3). The children ́s nutritional status was assessed by: weight for height; weight for age; and height for age. On all children with TAC and reliableness evaluation a clinical exam was performed and a paediatric clinic questionnaire was fi lled out. Results. The evaluation by pathological anatomy (n=5) as well as the computerized axial tomography as compared to thymus sonography did not show statistically signifi cant differences in the measurements of thymus size. In group 3 (n=15), the intraobserver correlation index was 0.96. Statistical analysis was performed using one-way ANOVA + test of a Scheffé and analysis of variance (ANOVA). Conclusion.The validity of the thymus sonography in children is adequate, it is a tool that “measures what it says it measures”. The intraobserver reliableness establishes an almost perfect correlation index in a well trained person for measuring thymus size by sonography in children.

Histologic and molecular assessment of human thymus.

Most work describing the histopathology of normal human thymus has focused on pediatric thymus because of tissue availability and high thymopoietic activity. However, pathologic examination of the thymus can provide information about immune status that is relevant to the clinical care of patients of all ages. Understanding age-related changes in the relative abundance and composition of anatomic compartments within the thymus is critical for evaluation of the thymus in normal adults and patients with diseases that affect the thymus. The purpose of this review is to acquaint diagnostic pathologists with some of the newer histologic, flow cytometric, and molecular techniques for assessment of non-neoplastic thymus. Diagnostic criteria are presented for assessment of thymic function and for determining the mechanisms underlying thymic hyperplasia. Accurate assessment of thymic function is critical for the diagnosis and treatment of patients with complete DiGeorge syndrome and can complement the clinical care of patients with a variety of disorders that affect the immune system.

Thymus size at birth is associated with infant mortality: a community study from Guinea-Bissau.

UNLABELLED: A few studies have suggested that thymus atrophy is associated with severe malnutrition and increased morbidity; however, no study of thymus size has been undertaken in countries with high mortality. This study examined the relation between thymus size at birth and subsequent mortality in an urban West African community. The size of the thymus was assessed by sonography as a volume estimate, the thymus index. A total of 278 children born at the local health centre in Bandim in Bissau, Guinea-Bissau, was enrolled in the study. Children were followed to the age of 2 y. Thymus size at birth was associated with most strongly weight, as well as with length and arm circumference. Controlling for weight and other risk factors, boys had larger thymus indices than girls [means ratio (MR) = 1.07, 95% confidence interval (95% CI) 1.01-1.14)]. Thymus size was also associated with prematurity, ethnic group, season and investigator, but not with birth order, mother's age, socioeconomic factors or the use of health services. Infant mortality was 117/1000. In a multivariate analysis, excluding premature infants and adjusting for age, gender, ethnic group, season of birth and investigator, higher birthweight (MR = 0.35, 95% CI 0.16-0.74) and larger thymus size (MR = 0.17, 95% CI 0.06-0.48) were independently associated with lower infant mortality. When both indices were estimated in the same model, the thymus index was associated with infant mortality (MR = 0.27, 95% CI 0.07-1.00), whereas birthweight had a non-significant effect (MR = 0.59, 95% CI 0.24-1.47). After 1 y of age neither birthweight nor thymus size at birth was associated with mortality. CONCLUSION: As all deaths were due to infectious diseases, thymus size at birth may be an important predictor of immune competence. Future studies should examine the determinants of thymus growth.

Non-invasive, quantitative assessment of the anatomical phenotype of corticotropin-releasing factor-overexpressing mice by MRI.

High resolution magnetic resonance imaging (MRI) was applied to quantify alterations in thymus and adrenal volumes, as well as body fat in genetically engineered corticotropin-releasing factor (CRF)-overexpressing mice. When compared to the organs in age-matched wild-type animals, the adrenals in CRF-overexpressing male mice were significantly enlarged and the thymus volume in females was significantly smaller. The fat content was significantly larger in CRF-overexpressing mice. The anatomical alterations observed in the MRI studies were in perfect line with post-mortem data (weights of organs). Furthermore, the observed interstrain differences are in agreement with recently published data on (i) the effect of continuous, intraventricular infusion of CRF in rats and (ii) the presence of atrophic adrenals in CRF-knockout mice. The present studies demonstrate that MRI can provide reliable measures of relatively small structures such as the adrenal glands and the thymus in mice. This makes MRI an attractive, non-terminal tool to monitor in laboratory animals, including transgenic mice, the consequence of continuous stress on relevant organs.

Morphometric assessment of thymic size variation in laboratory rabbits.

Sections of thymus from New Zealand white rabbits used as controls in 28-day and 91-day percutaneous toxicity studies conducted at different laboratories were morphometrically assessed. Measurements of total thymic area, medullary area, and cortical area were greater for 28-day vs 91-day studies conducted at a given laboratory, but varied from one laboratory to another. Relative thymic measurements (percent medulla, percent cortex, and medulla:cortex ratio) were similar for studies conducted at each laboratory and from one laboratory to another regardless of study duration. A decrease in thymic size occurred between approximately 16 and 25 weeks of age (i.e., 28-day studies vs 91-day studies) due to proportionally equivalent decreases in both the cortical and medullary areas. The consistency of the relative measurements can be used to assist in distinguishing changes in thymic size due to aging from changes in size due to stress or toxicity which would be expected to differentially affect the cortical and medullary areas. Appreciation of the normal variation in thymic size is needed when evaluating results of toxicity testing in rabbits. Data are provided as to the degree of normal variation of rabbit thymic size expected within and across percutaneous toxicity studies, with considerations for interpreting such data.

Normal thymus: assessment with MR and CT.

The magnetic resonance (MR) characteristics of the normal thymus in 18 patients were compared with computed tomographic (CT) findings in 13 of the 18. Patients ranged in age from 5 to 77 years. The thymus was visible in all patients and differed from subcutaneous fat in hydrogen density; the average thymus to fat hydrogen density ratio was 0.60. Although the T1 relaxation times of the thymus (mean = 703 msec) were much longer than those of fat (mean = 287 msec) in patients under 30 years of age, this difference decreased with age. The T2 relaxation times of the thymus were similar to those of fat and did not change with age. The thymus appeared thicker on MR images than on CT scans in patients older than 20 years. MR may be better than CT in distinguishing between thymus replaced by fat and mediastinal fat.

Longitudinal assessment of immunologic abnormalities of mice with the autosomal recessive mutation, "wasted".

Mice homozygous for the autosomal recessive mutation wasted (wst/wst) undergo a progressive wasting beginning at the third week of postnatal life, when body weight declines in the mutants. The wst/wst mice do not survive past 30 days of age. The present report describes histologic and functional abnormalities in a longitudinal analysis (17 to 29 days postpartum) of wst/wst mice. In addition to a marked age-dependent decline in wst/wst body weight as well as spleen and thymus wet weight to body weight ratios, we have observed a significant decline in spleen and thymus cell number in these organs, compared with phenotypically normal (+/+ or +/wst) littermates. Histologic analysis of the wst/wst thymus revealed marked cortical pyknosis at 23 days of age and significant cortical depletion by 26 days postpartum. The wst/wst spleen at 23 days of age and later was characterized by a marked reduction in the content of red pulp. Lymphoproliferative responsiveness to Con A was markedly altered in the wst/wst thymus and spleen, in an age-dependent fashion, compared with normal littermates. The wst/wst spleen LPS responsiveness was also markedly altered in an age-dependent fashion. Hypotheses are presented concerning the possible site(s) of gene action in the wst/wst mutant which may mediate the observed morphologic and functional abnormalities.